title: Kinetic response of a photoperturbed allosteric protein.
abstract: By covalently linking an azobenzene photoswitch across the binding groove of a PDZ domain, a conformational transition, similar to the one occurring upon ligand binding to the unmodified domain, can be initiated on a picosecond timescale by a laser pulse. The protein structures have been characterized in the two photoswitch states through NMR spectroscopy and the transition between them through ultrafast IR spectroscopy and molecular dynamics simulations. The binding groove opens on a 100-ns timescale in a highly nonexponential manner, and the molecular dynamics simulations suggest that the process is governed by the rearrangement of the water network on the protein surface. We propose this rearrangement of the water network to be another possible mechanism of allostery.
authors.affiliation: Department of Chemistry, University of Zurich, CH-8057 Zurich, Switzerland.
authors.forename: Brigitte
authors.initials: B
authors.lastname: Buchli
authors.forename: Steven A
authors.initials: SA
authors.lastname: Waldauer
authors.forename: Reto
authors.initials: R
authors.lastname: Walser
authors.forename: Mateusz L
authors.initials: ML
authors.lastname: Donten
authors.forename: Rolf
authors.initials: R
authors.lastname: Pfister
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blöchliger
authors.forename: Sandra
authors.initials: S
authors.lastname: Steiner
authors.forename: Amedeo
authors.initials: A
authors.lastname: Caflisch
authors.forename: Oliver
authors.initials: O
authors.lastname: Zerbe
authors.forename: Peter
authors.initials: P
authors.lastname: Hamm
mesh_terms: D000494:Allosteric Regulation / Q000502:physiology; D001391:Azo Compounds / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D007834:Lasers; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D010777:Photochemistry / Q000379:methods*; D011487:Protein Conformation; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13 / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013997:Time Factors; D014867:Water / Q000737:chemistry
chemical_list: D001391:Azo Compounds; D014867:Water; C516742:PTPN13 protein, human; D054595:Protein Tyrosine Phosphatase, Non-Receptor Type 13; C009850:azobenzene